Piperidine → 4-Acetyl-1-[3-[[2-[n-[6-(1-piperidinyl)pyridin-2-yl]amino]thiazol-5-yl]thio]benzoyl]piperazine

HRID 49143Notes

Reaction equation

HRID 49143 reaction equation
[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10](=[O:31])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([S:17][C:18]3[S:22][C:21]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26](Br)[N:25]=4)=[N:20][CH:19]=3)[CH:12]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2].[NH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1>CN(C)C1C=CN=CC=1.N1C=CC=CC=1>[C:1]([N:4]1[CH2:9][CH2:8][N:7]([C:10](=[O:31])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([S:17][C:18]3[S:22][C:21]([NH:23][C:24]4[CH:29]=[CH:28][CH:27]=[C:26]([N:32]5[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]5)[N:25]=4)=[N:20][CH:19]=3)[CH:12]=2)[CH2:6][CH2:5]1)(=[O:3])[CH3:2]

Participants

5

Reactant 2

HCID 8082PiperidineHCID 10301519HCID 10301519, compound

Product 1

HCID 103017264-Acetyl-1-[3-[[2-[n-[6-(1-piperidinyl)pyridin-2-yl]amino]thiazol-5-yl]thio]benzoyl]piperazineYield 83.1%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

A solution of Example 4 (30 mg, 0.058 mmol), piperidine (86 μL, 0.87 mmol), 4-dimethylaminopyridine (7.1 mg, 0.058 mmol) in pyridine (300 μL) was heated to 134° C. in a sealed vial under nitrogen for 8.75 h. Most of pyridine was removed on a speed-vac at 40° C. The residue was purified using reversed phase automated preparative HPLC (conditions: YMC S5 ODS A 20×100 mm column, 15 min gradient starting from 10% solvent B (90% MeOH, 10% H2O, 0.1% TFA) and 90% solvent A (10% MeOH, 90% H2O, 0.1% TFA) to 90% solvent B and 10% solvent A, flow rate 20 mL/min, λ=220 nM) to obtain the titled compound (25.2 mg, 68%) as a light tan solid.

Workup

  1. customMost of pyridine was removed on a speed-vac at 40° C
  2. customThe residue was purified
  3. customA 20×100 mm column, 15 min

Sources & evidence

ORD record
ord-bed2fe931b03499cb26d01d8f68d2a08
Source dataset
uspto-grants-2004_03
Patent number
US06706717B2

Reaction notes

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